Abstract：
BACKGROUND: The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety.
OBJECTIVE: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence.
METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results.
RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99 [95% CI 1.70, 2.32]). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%).
CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.
OBJECTIVE: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence.
METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results.
RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99 [95% CI 1.70, 2.32]). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%).
CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.
摘要：
背景：加巴喷丁在孕妇中的使用越来越普遍，这凸显了评估其新生儿安全性的必要性。
目的：本研究旨在通过一项队列研究和范围审查，对已发表的证据进行荟萃分析，调查加巴喷丁在妊娠期的胎儿安全性。
方法：我们在1995年至2019年期间使用马尼托巴健康数据库进行了一项基于人群的队列研究。我们研究了怀孕期间加巴喷丁使用与主要先天性畸形患病率之间的关系，心脏和口面部畸形,和新生儿重症监护病房（NICU）入院使用多元回归模型。我们在MEDLINE和EMBASE数据库中搜索了从开始到2022年10月的文献，以确定相关的观察性研究，并使用随机效应模型进行了荟萃分析。包括我们的队列研究结果。
结果：在289,227例怀孕中，870名孕妇接触加巴喷丁。妊娠早期加巴喷丁暴露与任何畸形风险增加无关（调整后的相对风险[aRR]）1.16（95％置信区间[CI]0.92，1.46），心脏畸形（RR1.29，95%CI0.72，2.29），口面部畸形（RR1.37，95%CI0.50，3.75），和主要的先天性畸形（RR1.00，95%CI0.73，1.36）。而在任何三个月的暴露与NICU入院风险增加相关(aRR，1.99[95%CI1.70，2.32]）。未调整结果的荟萃分析显示，重大先天性畸形的风险增加(RR1.44,95%CI1.28,1.61,I2=0%)。心脏畸形（RR1.66，95%CI1.11，2.47，I2=68%），和NICU入院（RR3.15，95%CI2.90，3.41，I2=10%），和口面畸形的增加趋势（RR1.98，95％CI0.79，5.00，I2=0％）。
结论：在队列研究和汇总荟萃分析中，使用加巴喷丁与NICU入院风险增加相关。临床医生应在怀孕期间谨慎使用加巴喷丁，需要进一步研究。
目的：本研究旨在通过一项队列研究和范围审查，对已发表的证据进行荟萃分析，调查加巴喷丁在妊娠期的胎儿安全性。
方法：我们在1995年至2019年期间使用马尼托巴健康数据库进行了一项基于人群的队列研究。我们研究了怀孕期间加巴喷丁使用与主要先天性畸形患病率之间的关系，心脏和口面部畸形,和新生儿重症监护病房（NICU）入院使用多元回归模型。我们在MEDLINE和EMBASE数据库中搜索了从开始到2022年10月的文献，以确定相关的观察性研究，并使用随机效应模型进行了荟萃分析。包括我们的队列研究结果。
结果：在289,227例怀孕中，870名孕妇接触加巴喷丁。妊娠早期加巴喷丁暴露与任何畸形风险增加无关（调整后的相对风险[aRR]）1.16（95％置信区间[CI]0.92，1.46），心脏畸形（RR1.29，95%CI0.72，2.29），口面部畸形（RR1.37，95%CI0.50，3.75），和主要的先天性畸形（RR1.00，95%CI0.73，1.36）。而在任何三个月的暴露与NICU入院风险增加相关(aRR，1.99[95%CI1.70，2.32]）。未调整结果的荟萃分析显示，重大先天性畸形的风险增加(RR1.44,95%CI1.28,1.61,I2=0%)。心脏畸形（RR1.66，95%CI1.11，2.47，I2=68%），和NICU入院（RR3.15，95%CI2.90，3.41，I2=10%），和口面畸形的增加趋势（RR1.98，95％CI0.79，5.00，I2=0％）。
结论：在队列研究和汇总荟萃分析中，使用加巴喷丁与NICU入院风险增加相关。临床医生应在怀孕期间谨慎使用加巴喷丁，需要进一步研究。
